20.6d Distribution

distributed

Once a medication has entered the bloodstream, it must be (?) throughout the body.

interstitial spaces

Most medications pass easily from the bloodstream through the (?) into the target cells.

albumin

Some medications, however, bind to proteins found in the blood—most commonly, (?)—and remain in the body for a prolonged time.

sustained release

They thus have a (?) from the bloodstream and a prolonged period of action.

unbound portion

The therapeutic effects of a medication are primarily due to the (?) of the medication in the blood.

plasma proteins

A medication that is bound to (?) cannot cross membranes and reach the target cells.

unbound medication

Thus, only the (?) is in equilibrium with the target cells and can cross the cell membranes.

pH

Changing the bloodstream’s (?) can affect a medication’s protein-binding action.

Tricyclic antidepressants (TCAs)

(?) for instance, are strongly bound to plasma proteins.

more alkaline

Making the blood (?) increases protein binding of the TCA molecules.

sodium bicarbonate

Therefore, in addition to supportive therapy, serious overdoses of TCAs are treated by administering (?).

raises the pH

It makes the blood more alkaline (?), causing increased binding of the TCA to serum proteins.

free drug

Cumulatively, this decreases the amount of (?) in the blood, thus decreasing the adverse effects.

elimination

Sodium bicarbonate administration also facilitates (?) of the medication through the urine.

serum protein-binding medications

The presence of other (?) can also affect medication–protein binding.

warfarin (Coumadin)

For example, the medication (?) is highly protein bound (99 percent).

1 percent

Its therapeutic effects are due to the (?) of the medication that is unbound and circulating in the bloodstream.

Aspirin

Aspirin molecules bind to the same binding site on the serum proteins as do warfarin molecules.

displaces

Thus, when aspirin is administered to a patient on warfarin, it (?) some of the protein-bound warfarin, increasing the amount of free (unbound) warfarin in the blood.

doubles

Even if it displaces only 1 percent of the total warfarin, it effectively (?) the available warfarin.

hemorrhage

This can lead to unwanted side effects, such as (?).

Albumin

(?) is one of the chief proteins in the blood available for binding with medications.

hypoalbuminemia

When albumin levels are low ((?)), as occurs in malnutrition, medications that are normally protein bound rise to much higher blood levels than anticipated.

dangerous bleeding

If the patient develops hypoalbuminemia, the normal dose of warfarin results in much more of the medication being available in the body, possibly leading to (?).

exclude

Certain organs (?) some medications from distribution.

blood–brain barrier

For example, the tight junctions of the capillary endothelial cells in the central nervous system (CNS) vasculature form a (?).

non-protein-bound, highly lipid-soluble medications

These cells are packed together so tightly that only (?) can cross into the CNS.

placental barrier

The so-called (?) can likewise prevent medications from reaching a fetus although it is not the solid barrier that its name implies.

almost every medication

The fetus is exposed to (?) that the pregnant woman takes.

lipid soluble, non-ionized, and non-protein-bound

However, because any medication must traverse the maternal blood supply and cross the capillary membranes into the placental (fetal) circulation, delivering medications to a fetus requires them to be (?).

placental transfer

This can slow some medications or reduce their (?) to benign levels.

deposited

Other medications are (?) in specific tissues.

medication depot

Fatty tissue, for example, can serve as a (?), or reservoir.

relatively stable depot

Because blood flow is lower in fatty areas than in muscular areas, fatty tissue is a (?), it can neither absorb nor release a large amount of medication in a short time.

tetracycline antibiotics

Similarly, bones and teeth can accumulate high amounts of medications, especially (?), that bind to calcium.